The role of extracellular matrix in normal and pathological pregnancy: Future applications of microphysiological systems in reproductive medicine

Abstract

<jats:p> Remodeling of extracellular matrix in the womb facilitates the dramatic morphogenesis of maternal and placental tissues necessary to support fetal development. In addition to providing a scaffold to support tissue structure, extracellular matrix influences pregnancy outcomes by facilitating communication between cells and their microenvironment to regulate cellular adhesion, migration, and invasion. By reviewing the functions of extracellular matrix during key developmental milestones, including fertilization, embryo implantation, placental invasion, uterine growth, and labor, we illustrate the importance of extracellular matrix during healthy pregnancy and development. We also discuss how maladaptive matrix expression contributes to infertility and obstetric diseases such as implantation failure, preeclampsia, placenta accreta, and preterm birth. Recently, advances in engineering the biotic–abiotic interface have potentiated the development of microphysiological systems, known as organs-on-chips, to represent human physiological and pathophysiological conditions in vitro. These technologies may offer new opportunities to study human fertility and provide a more granular understanding of the role of adaptive and maladaptive remodeling of the extracellular matrix during pregnancy. </jats:p><jats:sec><jats:title>Impact statement</jats:title><jats:p> Extracellular matrix in the womb regulates the initiation, progression, and completion of a healthy pregnancy. The composition and physical properties of extracellular matrix in the uterus and at the maternal–fetal interface are remodeled at each gestational stage, while maladaptive matrix remodeling results in obstetric disease. As in vitro models of uterine and placental tissues, including micro-and milli-scale versions of these organs on chips, are developed to overcome the inherent limitations of studying human development in vivo, we can isolate the influence of cellular and extracellular components in healthy and pathological pregnancies. By understanding and recreating key aspects of the extracellular microenvironment at the maternal–fetal interface, we can engineer microphysiological systems to improve assisted reproduction, obstetric disease treatment, and prenatal drug safety. </jats:p></jats:sec>

The association between clinical features at the time of non-hysteroscopic myomectomy before pregnancy and adverse obstetric and perinatal outcomes: a single-center retrospective cohort study

“…Insu cient recovery of the myometrium can also affect placental growth. 23 Accordingly, in our study, the placental weight was lower when the interval between myomectomy and subsequent pregnancy was less than 2 years. This study also showed that the shorter the interval time between myomectomy and subsequent pregnancy, the higher the risk of emergency delivery.…”

Organoid co-culture model of the cycling human endometrium in a fully-defined synthetic extracellular matrix reveals epithelial-stromal crosstalk

“…The ECM is an integral and dynamic component of the endometrial microenvironment that mediates cellular and tissue-level function. 56 To engineer a fully synthetic ECM capable of supporting physiologically relevant culture of endometrial cells in vitro, we leveraged a multi- omic analysis of ex vivo human endometrial biopsies to characterize ECM composition and cell- ECM interactions. Specifically, we utilized single cell RNA sequencing (scRNAseq, N=6), and proteomic (LC-MS/MS, N=11) datasets from donors that represented the distinct phases across the menstrual cycle.…”

Loss of Imprinting Control of the lncRNA <i>H19</i>-fetal Mitogen <i>IGF2</i> Gene Cluster in the Decidual Microenvironment of Patients With Idiopathic Spontaneous Miscarriages

“…The molecular mechanisms underlying the spontaneous loss of a pregnancy are unknown (28). Decidualization plays a critical role in the implantation of the embryo through a regulatory network that coordinates trophoblast invasion of the maternal decidua-myometrium and remodeling of maternal uterine spiral arteries (29,30).…”